Lactobacillus delbrueckii CIDCA 133 fermented milk modulates inflammation and gut microbiota to alleviate acute colitis.

Lactobacillus delbrueckii subsp. lactis CIDCA 133 is a health-promoting bacterium that can alleviate gut inflammation and improve the epithelial barrier in a mouse model of mucositis. Despite these beneficial effects, the protective potential of this strain in other inflammation models, such as inflammatory bowel disease, remains unexplored. Herein, we examined for the first time the efficacy of Lactobacillus delbrueckii CIDCA 133 incorporated into a fermented milk formulation in the recovery of inflammation, epithelial damage, and restoration of gut microbiota in mice with dextran sulfate sodium-induced colitis. Oral administration of Lactobacillus delbrueckii CIDCA 133 fermented milk relieved colitis by decreasing levels of inflammatory factors (myeloperoxidase, N-acetyl-ß-D-glucosaminidase, toll-like receptor 2, nuclear factor-κB, interleukins 10 and 6, and tumor necrosis factor), secretory immunoglobulin A levels, and intestinal paracellular permeability. This immunobiotic also modulated the expression of tight junction proteins (zonulin and occludin) and the activation of short-chain fatty acids-related receptors (G-protein coupled receptors 43 and 109A). Colonic protection was effectively associated with acetate production and restoration of gut microbiota composition. Treatment with Lactobacillus delbrueckii CIDCA 133 fermented milk increased the abundance of Firmicutes members (Lactobacillus genus) while decreasing the abundance of Proteobacteria (Helicobacter genus) and Bacteroidetes members (Bacteroides genus). These promising outcomes influenced the mice's mucosal healing, colon length, body weight, and disease activity index, demonstrating that this immunobiotic could be explored as an alternative approach for managing inflammatory bowel disease.

Recombinant probiotic Lactococcus lactis delivering P62 mitigates moderate colitis in mice.

Introduction and objective: p62 is a human multifunctional adaptor protein involved in key cellular processes such as tissue homeostasis, inflammation, and cancer. It acts as a negative regulator of inflammasome complexes. It may thus be considered a good candidate for therapeutic use in inflammatory bowel diseases (IBD), such as colitis. Probiotics, including recombinant probiotic strains producing or delivering therapeutic biomolecules to the host mucosal surfaces, could help prevent and mitigate chronic intestinal inflammation. The objective of the present study was to combine the intrinsic immunomodulatory properties of the probiotic Lactococcus lactis NCDO2118 with its ability to deliver health-promoting molecules to enhance its protective and preventive effects in the context of ulcerative colitis (UC). Material and methods: This study was realized in vivo in which mice were supplemented with the recombinant strain. The intestinal barrier function was analyzed by monitoring permeability, secretory IgA total levels, mucin expression, and tight junction genes. Its integrity was evaluated by histological analyses. Regarding inflammation, colonic cytokine levels, myeloperoxidase (MPO), and expression of key genes were monitored. The intestinal microbiota composition was investigated using 16S rRNA Gene Sequencing. Results and discussion: No protective effect of L. lactis NCDO2118 pExu:p62 was observed regarding mice clinical parameters compared to the L. lactis NCDO2118 pExu: empty. However, the recombinant strain, expressing p62, increased the goblet cell counts, upregulated Muc2 gene expression in the colon, and downregulated pro-inflammatory cytokines Tnf and Ifng when compared to L. lactis NCDO2118 pExu: empty and inflamed groups. This recombinant strain also decreased colonic MPO activity. No difference in the intestinal microbiota was observed between all treatments. Altogether, our results show that recombinant L. lactis NCDO2118 delivering p62 protein protected the intestinal mucosa and mitigated inflammatory damages caused by dextran sodium sulfate (DSS). We thus suggest that p62 may constitute part of a therapeutic approach targeting inflammation.

High-intensity interval training reduces monocyte activation in obese adults.

Alterations in the distribution and activation of monocyte subsets are frequently observed in individuals with obesity and their participation in the pathological complications of obesity is proposed. High-intensity interval training (HIIT) can be a time-efficient alternative to counteract the inflammatory outcomes of obesity, but so far, its effects on monocytes in obesity has not been fully explored. In this study, we investigated whether 8 weeks of HIIT can modify the distribution and activation of the three monocyte subsets (classical, intermediate and non-classical monocytes) in individuals with obesity. Our data show that individuals with obesity have a higher percentage of non-classical monocytes compared to control, lean individuals, and consequently an imbalance among the CD16+ monocyte subsets. Also, the expression of HLA-DR by intermediate monocytes is higher in insulin-resistant obese individuals, which indicates monocyte activation in obesity. After 8 weeks of HIIT, the percentage of non-classical monocytes was reduced in individuals with obesity, restoring the balance among the CD16+ monocytes. Also, the expression of HLA-DR by intermediate monocytes in insulin-resistant obese subjects was lower after HIIT. Both findings indicate that monocyte activation in individuals with obesity was reduced by HIIT. These modifications were observed in the absence of changes in weight and body composition, although they were accompanied by the improvement in the metabolic status (reduced insulin levels). Our findings indicate that HIIT can be considered a time-efficient strategy to manage obesity-related monocyte alterations and strengthen the immunomodulatory potential of HIIT.

IL-33 in obesity: where do we go from here?

IL-33 is a cytokine that belongs to the IL-1 family and is classically associated with type 2-like immune responses. In the adipose tissue, IL-33 is related to the beiging of adipocytes and to the maintenance of adipose tissue-resident immune cells, such as innate lymphoid cells 2, alternatively activated macrophages and regulatory T cells, which contribute to the maintenance of adipose tissue homeostasis. In the obese adipose tissue, the number of these cells is diminished, unlike the expression of IL-33, which is up-regulated. However, despite its increased expression, IL-33 is not able to maintain the homeostasis of the obese adipose tissue. IL-33 treatment, on the other hand, highly improves obesity-related inflammatory and metabolic alterations. The evidence that exogenous IL-33, but not adipose tissue-driven IL-33, regulates the inflammatory process in obesity leaves a gap in the understanding of IL-33 biology. Thus, in this review we discuss the potential mechanisms associated with the impaired action of IL-33 in obesity.